All living subjects maintain a reducing environment within their cells. However, due to the aerobic metabolism by the mitochondria and other factors, reactive oxygen-derived species such as peroxides and free oxygen radicals are produced. The reducing environment is preserved by enzymes such as superoxide dismutase, catalase and glutathion peroxidase. If the normal redox state is disturbed, the reactive oxygen species may damage all components of the cell, including protein, lipids and especially DNA. This imbalance between the production of reactive oxygen species and the ability to detoxify the reactive intermediates or repair the damage caused by the reactive oxygen species is called oxidative stress. In humans, oxidative stress is an important factor in aging and degenerative diseases associated with aging such as cancer, arthritis, diabetes, artherosclerosis, Lou Gehrig's disease, Parkinson's disease, heart failure, Alzheimers's disease, and Huntington's disease. The free-radical theory of aging states that organisms age because cells accumulate damage caused by reactive oxygen species over time.
In order to prevent the adverse effects of oxidative stress, there is a need for screening of dietary components which have anti-oxidative properties. Especially food grade bacteria, particularly lactic acid bacteria, are suitable anti-oxidative dietary components, since their use advantageously results in a long term effect of anti-oxidant action, via colonization of the intestinal tract.
The U.S. Pat. No. 6,884,415 discloses an antioxidant food product produced by fermenting a food product containing Lactobacillus plantarum having a superoxide dismutase (SOD)-like activity and a catalase (CAT) activity, in the presence of a manganese-containing natural material. Nevertheless, it is known that food grade bacteria, including lactic acid bacteria, can have anti-oxidative properties not dependent on the catalase or SOD activity.
The International Application WO 03/002131 discloses a Lactobacillus fermentum strain as anti-oxidative probiotic. The anti-oxidative properties of this strain were characterized in vitro by enzymatic tests and by measuring the glutathion red/ox potential.
The International Application WO 00/20013 discloses a Lactobacillus or Propionibacterium strain giving rise to increased amounts of propionic acid in the gut of a mammal for the manufacture of a medicament for reducing oxidative stress factors such as IL-6, reactive oxygen species and adhesion molecules.
Caenorhabditis elegans (C. elegans) is a free-living, transparent worm (nematode), which lives in temperate soil environments. C. elegans feeds on bacteria, particularly Escherichia coli OP50 strain. It has since been used extensively as a model organism for a variety of reasons. Strains are cheap and easy to breed and can be frozen. When subsequently thawed, they remain viable, allowing long-term storage. They have a short and reproducible life span. C. elegans has the advantage of being a multicellular eukaryotic organism that is simple enough to be studied in great detail. This worm has close to 40% of human orthologous genes among the whole genome, which make it an organism relevant for the human situation.
Caenorhabditis elegans has been used as animal model system for assessing the oxidative damage and effects on aging (Larsen, 1993, PNAS 90:8905-8909). The study has been carried out with a mutant strain having hyper-resistance to oxidative stress compared to its parental strain.
Further, Ikeda et al. (2007, AEM 73:6404-6409) have studied the effect of lactic acid bacteria on life span and Salmonella resistance of C. elegans. The authors suggest that C. elegans can be an appropriate model for screening probiotic bacteria strains (exerting beneficial effects on human health when ingested in sufficient numbers) or dietetic antiaging substances. However, resistance against oxidative stress was not assessed in this study. It is also known that the increased life span for C. elegans is related to the insulin pathway and related to orthologous genes in humans involved in the insulin-like growth factor and diabetes (Glenn et al., 2004, J Gerontol A Biol Sci Med Sci. 59:1251-1260).